Spatial and temporal microbial pollution patterns in a tropical estuary during high and low river flow conditions.

Spatial and temporal patterns of coastal microbial pollution are not well documented. Our study examined these patterns through measurements of fecal indicator bacteria (FIB), nutrients, and physiochemical parameters in Hilo Bay, Hawai'i, during high and low river flow. >40% of samples tested positive for the human-associated Bacteroides marker, with highest percentages near rivers. Other FIB were also higher near rivers, but only Clostridium perfringens concentrations were related to discharge. During storms, FIB concentrations were three times to an order of magnitude higher, and increased with decreasing salinity and water temperature, and increasing turbidity. These relationships and high spatial resolution data for these parameters were used to create Enterococcus spp. and C. perfringens maps that predicted exceedances with 64% and 95% accuracy, respectively. Mapping microbial pollution patterns and predicting exceedances is a valuable tool that can improve water quality monitoring and aid in visualizing FIB hotspots for management actions.

Alterations in Memory and Impact on Academic Outcomes in Children Following Allogeneic Hematopoietic Cell Transplantation.

The prevalence of late effects following allogeneic hematopoietic cell transplantation (HCT), a curative treatment for pediatric leukemia, is high: 79% of HCT recipients experience chronic medical conditions. The few extant studies of cognitive late effects have focused on intelligence and are equivocal about HCT neurotoxicity. In an archival study of 30 children (mean transplant age = 6 years), we characterize neuropsychological predictors of academic outcomes. Mean intellectual and academic abilities were average, but evidenced extreme variability, particularly on measures of attention and memory: ∼25% of the sample exhibited borderline performance or lower. Medical predictors of outcome revealed paradoxically better memory associated with more severe acute graft-versus-host disease (GVHD) and associated with steroid treatment. Processing speed and memory accounted for 69% and 61% of variance in mathematics and reading outcomes, respectively. Thus, our findings revealed neurocognitive areas of vulnerability in processing speed and memory following HCT that contribute to subsequent academic difficulties.

Preclinical development of AMG 139, a human antibody specifically targeting IL-23.

BACKGROUND AND PURPOSE: AMG 139 is a human anti-IL-23 antibody currently in a phase II trial for treating Crohn's disease. To support its clinical development in humans, in vitro assays and in vivo studies were conducted in cynomolgus monkeys to determine the pharmacology, preclinical characteristics and safety of this monoclonal antibody. EXPERIMENTAL APPROACH: The in vitro pharmacology, pharmacokinetics (PK), pharmacodynamics and toxicology of AMG 139, after single or weekly i.v. or s.c. administration for up to 26 weeks, were evaluated in cynomolgus monkeys. KEY RESULTS: AMG 139 bound with high affinity to both human and cynomolgus monkey IL-23 and specifically neutralized the biological activity of IL-23 without binding or blocking IL-12. After a single dose, linear PK with s.c. bioavailability of 81% and mean half-life of 8.4-13 days were observed. After weekly s.c. dosing for 3 or 6 months, AMG 139 exposure increased approximately dose-proportionally from 30 to 300 mg·kg(-1) and mean accumulation between the first and last dose ranged from 2- to 3.5-fold. Peripheral blood immunophenotyping, T-cell-dependent antigen responses and bone formation markers were not different between AMG 139 and vehicle treatment. No adverse clinical signs, effects on body weight, vital signs, ophthalmic parameters, clinical pathology, ECG, organ weights or histopathology were observed in the monkeys with the highest dose of AMG 139 tested (300 mg·kg(-1) s.c. or i.v.). CONCLUSIONS AND IMPLICATIONS: The in vitro pharmacology, PK, immunogenicity and safety characteristics of AMG 139 in cynomolgus monkeys support its continued clinical development for the treatment of various inflammatory diseases.

A qualitative study of persons who are 100% adherent to antiretroviral therapy.

This qualitative study examined the medication-taking behaviors and attitudes of participants determined to be 100% adherers to antiretroviral therapy from a NIH-funded study testing a 12-week telephone adherence intervention. Using open-ended questions, interviewers collected data on a sample of 13 informants, whose medication adherence to a randomly selected antiretroviral medication was 100%, based on a 30-day data collection using electronic event monitoring (EEM). The analysis revealed 'successful medication management' as the core category or main theme. The participants achieved success with medication adherence through managing specific areas (regimen, self and environment). By adopting realistic expectations and pragmatic attitudes, adherence is fostered when medication taking is a priority, when patients believe in the efficacy of their medications and when there is a strong patient/provider relationship. Future research is needed to develop tailored interventions using strategies identified by this population. Further in-depth examination of medication-taking behaviors in 100% adherers may be useful in developing individualized programs to maximize adherence to antiretroviral therapy in the clinical setting.

Depresión y aculturación en mujeres americanas mexicanas y americanas europeas / Depression and acculturation in Mexican American and European American women

El objetivo de este trabajo fue determinar la relación entre depresión y aculturación en mujeres méxico-americanas y mujeres europeo-americanas. Participaron 76 mujeres méxico-americanas y europeo-americanas de Kansas City. La depresión se midió con la escala Center of Epidemiological Studies Depression Scale y la aculturación fue determinada por el Olmedo Acculturation Inventory. Los resultados de dicho estudio están de acuerdo con la investigación existente que indica que las puntuaciones en la aculturación para las euro-americanas fueron significativamente más altas que los resultados para las méxico-americanas y que hubo puntuación significamente más alta para las méxicoamericanas de primera a tercera generación. Este estudio también está de acuerdo con los hallazgos que indican que las puntuaciones en depresión de las mujeres méxicoamericanas fueron más altas que las de las mujeres euroamericanas. Las puntuaciones no estuvieron afectadas por las diferencias demográficas, como lo fueron las puntuaciones de la aculturación. Además, no hubo relación significativa entre la aculturación y la depresión (AU)

Variable frequency bioimpedance instrumentation.

The design of instrumentation used to measure the bioimpedance of skin or tissue is presented. An inexpensive, component level approach, appropriate for use by researchers rather that commercial applications, is emphasized. The design and implementation process is thoroughly explained and design tradeoffs are discussed with relation to various applications. A validation of the implementation in hardware is presented and an example application to skin impedance topography is considered.

Physiologic responses to acupuncture point stimulation: a pilot study to evaluate methods and instrumentation.

The physiological responses to needle stimulation of an acupuncture point and a nearby control point were compared in six healthy participants. The electrocardiogram (ECG), respiration, and electrodermal response (EDR) were measured along with the times of needle insertion, interim needle stimulation and needle removal. In addition to the aforementioned, any relevant events such as movement of the subject, unexpected noise, etc were annotated.

Diferencias de género en síntomas depresivos entre adolescentes mexicanos / Gender differences in depressive symptoms among Mexican adolescents

La investigación existente sobre diferencias de género en síntomas depresivos entre adolescentes mexicanos está limitada a estudios realizados en la ciudad de México. El propósito de este estudio fue continuar la investigación sobre género y depresión entre hombres y mujeres adolescentes de otras partes de México. Los resultados de las puntuaciones de los dos grupos de adolescentes que participaron en el estudio indicaron la no existencia de diferencias significativas de género en depresión tal y como fue medida por la versión española del Center for Epidemiological Studies Depression Scale (CES-D). Estos hallazgos contradicen algún estudio previo sobre diferencias de género en depresión en adolescentes -investigaciones que estudiaron a adolescentes que vivían en países "desarrollados" versus "en vías de desarrollo". Se exploraron diversas explicaciones alternativas, incluyendo cómo el efecto de vivir en un país que se desarrolla rápidamente, tal como México, puede impactar en las variables de género y depresión en adolescentes mexicanos. Adicionalmente, se discuten variables tales como estrés, aculturación, características de personalidad basadas en el sexo e ideación suicida. Se recomienda investigación adicional acerca de la relación entre género y depresión entre adolescentes que viven en México (AU)

Analysis of pesticide runoff from mid-Texas estuaries and risk assessment implications for marine phytoplankton.

During 1993, estuarine surface water samples were collected from the mid-Texas coast (Corpus Christi to Port Lavaca, TX). Agricultural watershed areas as well as tidal creeks immediately downstream were chosen as sampling sites along with adjoining bay sampling stations. Collections were made throughout the growing season (February to October 1993) before and after periods of significant (> 1.25 cm) rainfall. All samples were initially screened for the presence of pesticides using enzyme-linked immunosorbent assay (ELISA) test kits (EnviroGard) for triazine herbicides and carbamate insecticides. All samples were extracted and then analyzed using gas chromatography (GC) for quantification of atrazine. Only samples testing positive for carbamate insecticides via ELISA were further extracted for GC analysis to quantify aldicarb and carbofuran. Additionally, laboratory toxicity tests using phytoplankton were examined from published, peer-reviewed literature and compared with the atrazine field levels found in Texas. Results of ELISA screening indicated the presence of triazine herbicides in nearly all samples (>93%). GC analysis further confirmed the presence of atrazine concentrations ranging from <0.01-62.5 microg/L. Screening tests also found detectable levels of carbamate insecticides (aldicarb and carbofuran) that were also confirmed and quantified by GC. Comparison of measured concentrations of atrazine compared with published toxicity tests results indicated that there was a potential environmental risk for marine/estuarine phytoplankton in surface waters of Texas estuaries, particularly when the chronic nature of atrazine exposure is considered.

African-American women's perceptions of mammography screening.

While mammography has been shown to decrease breast cancer mortality, many African-American women are not receiving annual screenings. African-American women's reasons for not having mammograms are not well understood. This study therefore surveyed 164 African-American women concerning barriers to mammography screening. Outreach coordinators in two urban and one rural site in Texas asked African-American women to complete a checklist about the barriers to mammography screening. The 23-item Mammography Barriers Checklist, which was developed based upon one of the author's clinical experience and the research literature, included both internal and external barriers to screening. Women in all three geographic areas identified fear of finding cancer and mammography cost as the most important reasons for not having mammograms. These results suggest that outreach strategies that address fears related to mammography screening and help women find low-cost mammography resources may be more effective than those focusing strictly on providing information.

Magnetic and electromagnetic field therapy.

There is increasing interest in the application of magnetic/electromagnetic fields for therapeutic purposes. Magnetotherapy provides non-invasive, safe and easy to apply methods to directly treat the site of injury, the source of pain and inflammation as well as other types of dysfunction. This review summarizes several decades of experience worldwide in studying biological and clinical effects initiated by various magnetic and electromagnetic fields. The physiological basis for tissue repair as well as physical principles of dosimetry and application of magnetic fields are discussed. An analysis of magnetic/electromagnetic stimulation is followed by a discussion of the advantage of magnetic field stimulation compared with electric current stimulation. Finally, the proposed mechanisms of action are discussed.

Anatomic site and interanimal variability in morphologic characteristics of bottlenose dolphin (Tursiops truncatus) skin likely to affect dermal absorption studies.

OBJECTIVE: To investigate anatomic site and interanimal variability in dolphin skin for use in development of models for cutaneous absorption studies. SAMPLE POPULATION: Skin from 30 healthy free-ranging bottlenose dolphins (17 males and 13 females grouped by age) and 10 captive males between 13 and 19 years old. PROCEDURE: Biopsy specimens were collected from the 10 male dolphins at 3 anatomic sites and from the 30 dolphins at 1 site; specimens were evaluated by light microscopy. Stratum externum thickness, minimal depth to the vasculature, and maximal epidermal depth were measured at 4 locations on 4 sequential sections. Comparisons of replicate measurements for 3 skin characteristics were made within and among anatomic sites, between dolphins of the same sex and approximate age, and across males and females of various ages. RESULTS: The stratum externum in male dolphins was thicker. Differences attributable to age and anatomic site were not significant. Variation attributable to differences in stratum externum thickness between dolphins was significant. Differences among body sites within the same dolphin were significant but were not consistent from dolphin to dolphin. Mean stratum externum thickness was not different between males of the 2 cohorts, but mean maximal epidermal depth and mean minimal depth to the vasculature were different. Variances within the 2 male cohorts were not significantly different. CONCLUSIONS: Studies affected by stratum externum thickness should eliminate the effect attributable to sex difference by using dolphins of the same sex or grouping analytical data by sex. Precision could be improved without increasing the total number of dolphins by collecting more than 1 sample/dolphin.

Transactivation by the E2 protein of oncogenic human papillomavirus type 31 is not essential for early and late viral functions.

The activation of transcription and of DNA replication are, in some cases, mediated by the same proteins. A prime example is the E2 protein of human papillomaviruses (HPVs), which binds ACCN6GGT sequences and activates heterologous promoters from multimerized binding sites. The E2 protein also has functions in replication, where it complexes with the virally encoded origin recognition protein, E1. Much of the information on these activities is based on transient-transfection assays as well as biochemical analyses; however, their importance in the productive life cycle of oncogenic HPVs remains unclear. To determine the contributions of these E2 functions to the HPV life cycle, a genetic analysis was performed by using an organotypic tissue culture model. HPV type 31 (HPV31) genomes that contained mutations in the N terminus of E2 (amino acid 73) were constructed; these mutants retained replication activities but were transactivation defective. Following transfection of normal human keratinocytes, these mutant genomes were established as stable episomes and expressed early viral transcripts at levels similar to those of wild-type HPV31. Upon differentiation in organotypic raft cultures, the induction of late gene expression and amplification of viral DNA were detected in cell lines harboring mutant genomes. Interestingly, only a modest reduction in late gene expression was observed in the mutant lines. We conclude that the transactivation function of E2 is not essential for the viral life cycle of oncogenic HPVs, although it may act to moderately augment late expression. Our studies suggest that the primary positive role of E2 in the viral life cycle is as a replication factor.

An STS-based map of the human genome.

A physical map has been constructed of the human genome containing 15,086 sequence-tagged sites (STSs), with an average spacing of 199 kilobases. The project involved assembly of a radiation hybrid map of the human genome containing 6193 loci and incorporated a genetic linkage map of the human genome containing 5264 loci. This information was combined with the results of STS-content screening of 10,850 loci against a yeast artificial chromosome library to produce an integrated map, anchored by the radiation hybrid and genetic maps. The map provides radiation hybrid coverage of 99 percent and physical coverage of 94 percent of the human genome. The map also represents an early step in an international project to generate a transcript map of the human genome, with more than 3235 expressed sequences localized. The STSs in the map provide a scaffold for initiating large-scale sequencing of the human genome.

Integration of physical, breakpoint and genetic maps of chromosome 22. Localization of 587 yeast artificial chromosomes with 238 mapped markers.

Detailed physical maps of the human genome are important resources for the identification and isolation of disease genes and for studying the structure and function of the genome. We used data from STS content mapping of YACs and natural and induced chromosomal breakpoints to anchor contigs of overlapping yeast artificial chromosome (YAC) clones spanning extensive regions of human chromosome 22. The STSs were assigned to specific regions (bins) on the chromosome using cell lines from a somatic hybrid mapping panel defining a maximum of 25 intervals. YAC libraries were screened by PCR amplification of hierarchical pools of yeast DNA with 238 markers, and a total of 587 YAC clones were identified. These YACs were assembled into contigs based upon their shared STS content using a simulated annealing algorithm. Fifteen contigs, containing between 2 and 74 STSs were assembled, and ordered along the chromosome based upon the cytogenetic breakpoint, meiotic and PFG maps. Additional singleton YACs were assigned to unique chromosomal bins. These ordered YAC contigs will be useful for identifying disease genes and chromosomal breakpoints by positional cloning and will provide the foundation for higher resolution physical maps for large scale sequencing of the chromosome.

Isolation and regional mapping of 110 chromosome 22 STSs.

As part of a larger effort to create a complete physical map of the human genome, we have developed 110 new STSs specific for human chromosome 22. Clones isolated and sequenced from chromosome 22-enriched libraries provided a source of primers. These STSs were localized to regions of chromosome 22 using a panel of somatic cell hybrids. In building a refined physical map of chromosome 22, this set of STSs should provide a substantial backbone.

16S rRNA phylogenetic analysis of the bacterial endosymbionts associated with cytoplasmic incompatibility in insects.

Bacterial endosymbionts of insects have long been implicated in the phenomenon of cytoplasmic incompatibility, in which certain crosses between symbiont-infected individuals lead to embryonic death or sex ratio distortion. The taxonomic position of these bacteria has, however, not been known with any certainty. Similarly, the relatedness of the bacteria infecting various insect hosts has been unclear. The inability to grow these bacteria on defined cell-free medium has been the major factor underlying these uncertainties. We circumvented this problem by selective PCR amplification and subsequent sequencing of the symbiont 16S rRNA genes directly from infected insect tissue. Maximum parsimony analysis of these sequences indicates that the symbionts belong in the alpha-subdivision of the Proteobacteria, where they are most closely related to the Rickettsia and their relatives. They are all closely related to each other and are assigned to the type species Wolbachia pipientis. Lack of congruence between the phylogeny of the symbionts and their insect hosts suggest that horizontal transfer of symbionts between insect species may occur. Comparison of the sequences for W. pipientis and for Wolbachia persica, an endosymbiont of ticks, shows that the genus Wolbachia is polyphyletic. A PCR assay based on 16S primers was designed for the detection of W. pipientis in insect tissue, and initial screening of insects indicates that cytoplasmic incompatibility may be a more general phenomenon in insects than is currently recognized.

Ventilator dependency: decision-making, daily functioning and quality of life for patients with Duchenne muscular dystrophy.

Ventilator assistance is offered to patients with Duchenne muscular dystrophy as an option to extend life. This paper discusses the effect of respiratory difficulties and the subsequent quality of life for 17 patients and 14 family members living in the community. Areas covered included decision-making, health, education, vocational and recreational status, community resources and life satisfaction. Activity levels before and after ventilator use were assessed. Despite restrictions in daily life both before and after ventilator use, quality of life was fairly good. Restrictions in daily life were caused by a combination of progression of the disease and the ventilator, and family members were more burdened by the ventilator than were patients. It is concluded that patients and their families should make the decision about accepting or rejecting assisted ventilation.